Antigen distortion allows influenza virus to escape neutralization.
The structure of the hemagglutinin (HA) of a mutant influenza virus that escapes neutralization by a monoclonal antibody shows that the mutation causes changes in HA structure which avoid an energetically less favorable conformation. However, the structure of the mutant HA.Fab complex indicates that the antibody binds selectively to mutant HA in a wild type-like distorted conformation. The association of an antibody with a less favored HA conformation represents an alternative to previously described mechanisms of escape from neutralization by antibodies.
Fleury
D
D
Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Gif-sur-Yvette, France.
Wharton
S A
SA
Skehel
J J
JJ
Knossow
M
M
Bizebard
T
T
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D007140:Immunoglobulin Fab Fragments; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007140:Immunoglobulin Fab Fragments